{{B}}Scientists Watch the Biological Clock at Work{{/B}}
Inside a small chamber at a Kent State University laboratory, hamsters sleep, eat, play and rest while fluid flows in and out of tubes threaded through their tiny brains. It took biology professor J. David Glass two years to set up the finicky dialysis system, which measures a key neurotransmitter in the biological clocks of these nocturnal rodents. His payoff came in 1996, when he became tile first researcher to measure serotonin levels rising and falling in the biological clock area of the brain during an animal's daily cycle. Serotonin is the "feel good" chemical manipulated by widely prescribed drugs such as Prozac.
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Glass's research and that of others could have implications for the millions of people who take common anti-depressants and other drugs that affect serotonin in the brain. It has long been known that the substance is a key player in the biological clock, and that the region has an unusually high concentration of receptors for the neurotransmitter.
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Like other animals and even plants, humans have built-in clocks that regulate internal functions on a 24-hour basis. For most mammals, the clocks trigger sleep and waking, as well as metabolism, hormone levels, body temperature and many other changes.
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Sitting on top of the optic nerve, the clock is heavily influenced by light. But other factors, too, are involved in resetting the mechanism, most notably physical activity and substances like serotonin. Glass and his students found that, when lights in the hamster Chamber were switched off, the serotonin levels in the rodents' clock region shot up: hamsters are nocturnal, meaning they rest during the day and are awake at night: But when hamsters in the midst of their sleep cycle were put onto an activity wheel, a significant rise in serotonin levels was measured in those hamsters that woke up enough to exercise.
It has long been known that serotonin is key to body clock function, according to Thomas Wehr, a scientist with the National Institute of Mental Health in Bethesda, Maryland. Researchers at the Maryland Institute took cells from the clock region of the brain, sprinkled serotonin on them and, by monitoring electrical impulses, watched the cells "reset" themselves.
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Studies have found that serotonin affects the clock in different ways, depending on the point in the cell's daily cycle that it is administered. Glass recently completed an experiment using marmosets, small monkeys native to Central and South America. Researchers moved a sleeping marmoset to another cage, then monitored it as it scurried around its new environment. After this burst of activity, the marmoset shifted its cycles forward or backward a few hours, and they remained shifted, apparently indefinitely. Cycles were pushed back when the disruption occurred early in the sleep period; they shifted forward when the disruption occurred late in the cycle.
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A. According to Glass, the experiment demonstrates what scientists have known anecdotally for a long time: that exercise, when performed at certain times, shifts our clocks. Exercise has long been recommended to speed recovery from jet lag, for example. That may he because exercise boosts sero-tonin. Glass found he could mimic the effect of the arousal experiment by injecting a sero-toninlike drug and believes the findings suggest something similar could be expected in people. "We're getting closer and closer to making the link that humans can adjust their circadian clock through natural means such as exercise," Glass says.
B. "There are certain drugs used with humans that have also been squirted on these cells in dishes and have been shown to reset the clock in the dish, so it seems quite possible there are similar effects in humans who take these drugs. "Wehr says. Indeed, some people taking antidepressants do report sleep disorders such as insomnia or daytime drowsiness that could be related to changes in their biological clocks. Human studies have yet to focus on the issue.
C. Later scientists wondered about circadian rhythms in humans. They learned that man's biological clock actually keeps time with a day of a little less than 25 hours instead of the 24 hours on a man-made clock.
D. Glass's work is part of the fast-growing field of circadian (or daily) rhythm research focused on a region at the base of the brain, the size of a corn kernel, that scientists discovered 25 year ago is the body's timing mechanism.
E. Meanwhile, in a larger chamber down the hall, Glass is monitoring tropical monkeys. He has found that exercise and arousal from sleep have major impacts on the biological rhythms of the monkeys, permanently shifting their clocks in the absence of normal daylight and darkness cues.
F. This is a particularly exciting time for circadian-rhythm researchers. In recent times, scientists at universities in Illinois, Texas and Japan have found genes involved with the clock, including one that appears to be a basic building block of the mechanism and is common across all species, from fruit flies to humans. Meanwhile, researchers like Glass, whose work has attracted US